The Printed Circuit Heat Exchanger (PCHE) is considered promising as an intermediate heat exchanger for Molten Salt Reactors (MSRs) due to its highly compact construction, high heat transfer effectiveness, and capability of withstanding high pressures. In this study, thermal-mechanical simulations were performed using a two-channel unit-cell model with the attempt to investigate the structural integrity of a laboratory-scale PCHE that was designed for molten salt-to-supercritical carbon dioxide heat transfer, with the temperature field obtained from Computational Fluid Dynamics (CFD) simulations. It is shown that the fillets on the semi-circular channel walls are stress concentration regions and that the stress intensity decreases quickly as the distance from the fillets increases. A quick drop in the maximum stress intensity is observed with the increase of the fillet radius. There is no significant increase in the stress intensity for locations around the zigzag sharp corners. With a lower bulk temperature and a higher stress intensity, the region close to the outlet of the PCHE hot channels is more vulnerable to potential failures than the inlet region of the hot channels. In addition, the choice of channel models has a weak impact on the maximum stress intensity around the cold channel fillets.